Hsa_circ_0008234 facilitates proliferation of cutaneous squamous cell carcinoma through targeting miR-127-5p to regulate ADCY7.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignant tumor with 25-50% of 5-year survival. There exist urgent needs for the identification of novel biomarkers for the diagnostic and therapeutic strategies of cSCC. The differentially expressed circRNAs in cSCC tissues and non-lesional skin tissues were obtained through analyzing the circular RNAs (circRNAs) microarray dataset GSE74758. The expression pattern of the indicated circRNAs in cSCC tissues was confirmed by qRT-PCR. FISH analysis was used to detect the location of hsa_circ_0008234 in cells. RIP experiment was used to detect the interaction between hsa_circ_0008234 and miR-127-5p. CCK-8 analysis and colony formation assay were used to detect the proliferation of cSCC cells. qRT-PCR and western blot were adopted to detect the expression of ACDY7. Three differential expressed circRNAs were obtained from the microarray data (GSE74758), and hsa_circ_0008234 was confirmed to be highly expressed in cSCC tissues by qRT-PCR. Hsa_circ_0008234 was mainly located in cytoplasm and stable in cSCC cells. RIP experiment revealed that hsa_circ_0008234 directly interacts with miR-127-5p in cSCC cells. Hsa_circ_0008234 increased the cell viability and colony formation of cSCC cells through acting as the sponge of miR-127-5p. MiR-127-5p inhibited the expression of ADCY7 in cSCC cells through binding the 3'UTR of ADCY7. Hsa_circ_0008234 was positively associated with ADCY7 expression in cSCC tissues. Hsa_circ_0008234 facilitates the proliferation of cSCC through targeting miR-127-5p to regulate ADCY7 expression and has the potential to be a novel therapeutic target for cSCC.

Cai L ，Wang Y ，Wu J ，Wu G ... -  《-》

Circular RNA circ-LARP1B contributes to cutaneous squamous cell carcinoma progression by targeting microRNA-515-5p/TPX2 microtubule nucleation factor axis.

Wang L ，Hou S ，Li J ，Tian T ，Hu R ，Yu N ... -  《-》

Circ_0001402 knockdown suppresses the chemoresistance and development of DDP-resistant cutaneous squamous cell carcinoma cells by functioning as a ceRNA for miR-625-5p.

Cutaneous squamous cell carcinoma (CSCC) is the most common metastatic skin cancer. Circular RNAs (circRNAs) are differentially expressed in CSCC and can sequester and sponge microRNAs. GSE74758 shows that hsa_circ_0001402 (circ_0001402) is the most overexpressed circRNA in CSCC. Expression of circ_0001402, microRNA(miR)-625-5p and karyopherin subunit alpha 4 (KPNA4) was detected by quantitative real-time polymerase chain reaction and/or Western blot. Colon formation, flow cytometry, Transwell assays and xenograft tumour model confirmed the development of CSCC cells. The competing endogenous RNA (ceRNA) interaction was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Circ_0001402 was significantly upregulated in CSCC tissues and cells, and higher expression of circ_0001402 was found in DDP-resistant samples. Functionally, circ_0001402 knockdown induced apoptosis and inhibited half maximal inhibitory concentration of DDP, colony formation, migration and invasion of DDP-resistant CSCC cells, accompanied with the depressed multi-drug resistance-1 (MDR1) and MDR-related protein-1, while miR-625-5p inhibitor could counteract these effects. Mechanically, circ_0001402 mediated the expression regulation of KPNA4 via functioning as a ceRNA for miR-625-5p. KPNA4 re-expression could abate the functions of miR-625-5p. Furthermore, circ_0001402 knockdown could hinder tumour growth of DDP-resistant CSCC. Circ_0001402 knockdown can suppress the development and chemoresistance of DDP-resistant CSCC cells at least partly through targeting miR-625-5p/KPNA4 axis.

Li M ，Luo M ，Liu P ，Wang R ，Jing H ... -  《-》

Hsa_circ_0005085 may suppress cutaneous squamous cell carcinoma growth and metastasis through targeting the miR-186-5p/LAMC1 axis.

Cutaneous squamous cell carcinoma (CSCC) is a severe malignancy derived from the skin. Mounting evidence suggests that circular RNAs (circRNAs) participate in diverse biological functions in human cancers, containing CSCC. However, the biological functions and underlying mechanism of hsa_circ_0005085 in CSCC have not been clearly studied. Expression levels of hsa_circ_0005085, microRNA-186-5p (miR-186-5p), and Laminin subunit gamma 1 (LAMC1) were detected by reverse transcription-quantitative polymerase chain reaction. Cell counting kit-8 assay, colony formation assay, and 5-Ethynyl-2'-deoxyuridine assay were used to assess cell proliferation. Transwell assay was conducted to detect cell migration and invasion. Cell apoptosis was analyzed by flow cytometry. Protein expression of LAMC1, E-cadherin, Snail, and slug were assessed using western blot assay. Using bioinformatics software, the binding between miR-186-5p and hsa_circ_0005085 or LAMC1 was predicted, followed by verification using a dual-luciferase reporter and RNA-Immunoprecipitation. The mouse xenograft model was established to investigate the role of hsa_circ_0005085 in vivo. Hsa_circ_0005085 level was downregulated in CSCC tissues and cells. Overexpression of hsa_circ_0005085 inhibited cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in CSCC. MiR-186-5p could restore the effect of hsa_circ_0005085 overexpression on CSCC cells, and the knockdown of LAMC1 reversed the regulation of the miR-186-5p inhibitor. In mechanism, hsa_circ_0005085 served as a sponge for miR-186-5p to regulate LAMC1 expression. Overexpression of hsa_circ_0005085 reduced growth of tumor via miR-186-5p/LAMC1 axis in vivo. In our study, hsa_circ_0005085 might inhibit CSCC development by targeting the miR-186-5p/LAMC1 axis, which might provide a promising therapeutic target for CSCC.

Wang L ，Liu Y ，Gao Q ，Hu R ... -  《-》

Upregulated circular RNA circ_0070934 facilitates cutaneous squamous cell carcinoma cell growth and invasion by sponging miR-1238 and miR-1247-5p.

Accumulating studies have appreciated circular RNAs (circRNAs) as novel prognostic biomarkers and therapeutic targets in malignant carcinomas. Here, we aim to investigate the expression of a novel circRNA, circ_0070934. The biological roles and mechanisms of circ_0070934 in cutaneous squamous cell carcinoma (CSCC) were explored. The expression of circ_0070934 in CSCC tissues and cell lines was evaluated by qRT-PCR. Loss-of-function and gain-of-function assays were performed to detect cell proliferation, apoptosis, migration and invasion in vitro. Moreover, the underlying molecular mechanism of circ_0070934 was predicted by online database and luciferase reporter assay. Abnormally overexpression of circ_0070934 was detected in CSCC samples and cell lines. Inhibition of cell proliferation, invasion, migration, and increased apoptosis were observed upon circ_0070934 knockdown. The opposite effect was observed in the circ_0070934 overexpression cells. Circ_0070934 expression was negatively correlated with miR-1238 and miR-1247-5p expression in CSCC and luciferase reporter experiment verified the binding ability between circ_0070934 and miR-1238/miR-1247-5p. Rescue experiments further identified that the oncogenic role of circ_0070934 is attributed to its suppression of miR-1238 and miR-1247-5p. Taken together, our results implicate that circ_0070934 is correlated with tumor aggressiveness by serving as an oncogenic circRNA in CSCC.

An X ，Liu X ，Ma G ，Li C ... -  《-》